Applications of clinical decision support systems (CDSS) have become essential for physicians seeking to make appropriate decisions. The implementation of CDSS, however, is complicated if the factors affecting physician’s acceptance are not recognised. This study aims to explore the various factors that may influence the acceptance of CDSS in Saudi Arabia. A qualitative method was used to collect data from interviews with 54 GPs, with interviews conducted in three stages. The study then integrated the Unified Theory of Acceptance and Use of Technology (UTAUT) and Task-Technology Fit (TTF) models to communicate the findings. It is suggested that all factors of both UTAUT and TTF influence acceptance of CDSS by GPs, with the sole exception of the social influence factor. Some additional factors were also discovered by means of in-depth interviews, including accessibility, patient satisfaction, informativeness (increased knowledge), connectedness (informing patients), communication and shared knowledge, privacy and security, and perceived risk (functional performance risk and time risk). The study thus offers a new insight of the factors influencing GPs’ acceptance of CDSS.